Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines

Abstract

Objective To study the effect of carboxyamidotriazole-orotate(CTO) on the proliferation and fatty acid anabolism regulation of human pancreatic cancer cells. Methods Human pancreatic cancer cell lines AsPC-1, AsPC-1/GEM(AR), PANC-1 and MiaPaCa-2 were used as the study subjects; cell survival rate was detected by sulfonylrhodamine B(SRB); the mRNA level of key genes for fatty acid synthesis was detected by qPCR; the protein level of the AMPK/ACC pathway was detected by Western blot; intracellular lipid metabolites were examined by liquid chromatography-mass spectrometry(LC-MS). Results Comparing to control group, CTO significantly decreased the cell viability of AsPC-1, AR, PANC-1, and MiaPaCa-2(P＜0.05). CTO down-regulated the mRNA level of key fatty acid synthesis genes(P＜0.05). CTO significantly reduced the protein expression of AMPK, ACC and c-Myc(P＜0.05), while increasing the protein expression of p-AMPK and p-ACC(P＜0.05). CTO decreased lipid metabolite content in AR cells(P＜0.05). Conclusions CTO attenuates cellular fatty acid anabolism by inhibition of oncogene c-Myc expression and AMPK/ACC pathway, down-regulates the expression of fatty acid synthesis-related genes, and then inhibits proliferation of the human pancreatic cancer cell lines AsPC-1, AR, PANC-1 and MiaPaCa-2.

Keywords

• carboxyamidotriazole-orotate|pancreatic cancer|proliferation|fatty acid anabolism